chr1-207526921-C-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000651.6(CR1):c.1055C>G(p.Thr352Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00040 ( 3 hom., cov: 17)
Exomes 𝑓: 0.000053 ( 18 hom. )
Failed GnomAD Quality Control
Consequence
CR1
NM_000651.6 missense
NM_000651.6 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: -1.46
Genes affected
CR1 (HGNC:2334): (complement C3b/C4b receptor 1 (Knops blood group)) This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The genome is polymorphic at this locus with allele-specific splice variants encoding different isoforms, based on the presence/absence of long homologous repeats (LHRs). The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in this gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus, sarcoidosis and Alzheimer's disease. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.031938016).
BP6
?
Variant 1-207526921-C-G is Benign according to our data. Variant chr1-207526921-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2394007.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome at 4 BG gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CR1 | NM_000651.6 | c.1055C>G | p.Thr352Arg | missense_variant | 6/47 | ENST00000367049.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CR1 | ENST00000367049.9 | c.1055C>G | p.Thr352Arg | missense_variant | 6/47 | 5 | NM_000651.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 45AN: 113470Hom.: 3 Cov.: 17 FAILED QC
GnomAD3 genomes
?
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45
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17
FAILED QC
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GnomAD3 exomes AF: 0.000135 AC: 13AN: 96378Hom.: 4 AF XY: 0.0000793 AC XY: 4AN XY: 50432
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000527 AC: 71AN: 1348200Hom.: 18 Cov.: 30 AF XY: 0.0000373 AC XY: 25AN XY: 669420
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000396 AC: 45AN: 113520Hom.: 3 Cov.: 17 AF XY: 0.000497 AC XY: 27AN XY: 54360
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.0
.;.;.;B
Vest4
MVP
MPC
2.0
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at